The general aims are (1) to maintain a group of clinical and laboratory investigators who can interrelate their research on problems that relate directly ot cerebrovascular disease and (2) to provide and environment for training individuals for careers of leadership in research, training and clinical service in cerebrovascular diseases. Clinical investigation will include epidemiological studies on trends of incidence, prevalence, and survival in stroke in a population and studies that relate to triage, functional dependency and management for stroke. Natural history of carotid occlusive lesions and effect of cigarette smoking on development of carotid occlusive disease will be studied. A clinical trial of treatment of transient ischemic attacks will be done. There will be an evaluation of the sensitivity of proton nuclear magnetic resonance (NMR) tomography in the detection of cerebral ischemic lesions, particulary in early stages of ischemia and the findings on proton NMR tomography will be correlated with biochemical alterations in ischemic areas of human brains. There will be laboratory studies of the manner in which cerebral blood flow is coupled to metabolism in normal brain and of the pathophysiology of vasospasm following subarachnoid hemmorrahage or following ischemia. Other laboratory studies will use in vivo and in vitro models of cerebral ischemia and anoxia to investigate the temporal sequence of pathophysiologic changes at the molecular level to determine the factor(s) responsible for irreversibility of the processes and to attempt to modify the irreversible process by pharmacological agents.